Assessment of Adipocyte Function in Women with PCOS

多囊卵巢综合症女性脂肪细胞功能的评估

• 批准号: 7334641
• 负责人: DAVID A EHRMANN
• 金额: $ 18.84万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7334641
• 关键词: 11p; Address; Adenoviruses; Adipocytes; Adipose tissue; Affect; Age; Agonist; American; Androgens; Beta Cell; Biological Assay; Biopsy; Blood specimen; Body mass index; Branched-Chain Amino Acids; Breathing; Cardiovascular Diseases; Collaborations; Complement; Complex; Condition; Consumption; Continuous Positive Airway Pressure; Cortisone; Data; Development; Disease; Dyslipidemias; Elevation; Energy Metabolism; Enzymes; Estrogens; Event; Excision; Family; Fatty acid glycerol esters; Feeding behaviors; Gender; Glucocorticoid Receptor; Glucocorticoids; Glucose; Glucose Intolerance; Gonadal Steroid Hormones; Health; Hepatic; Heritability; Hormonal; Hormones; Human; Hydrocortisone; Hypertension; Immunoblotting; Impairment; In Vitro; Incidence; Insulin; Insulin Resistance; Intervention; Kinetics; Laboratories; Leptin; Leuprolide; Lipids; Lipolysis; Liver; Localized; Luciferases; Measures; Mediation; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Methodology; Molecular; Muscle; Mutation; Nonesterified Fatty Acids; Numbers; Obesity; Obstructive Sleep Apnea; Outcome; Ovarian; Ovarian Ablation; Pancreas; Pathogenesis; Pathologic; Pathology; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Plasma; Play; Polycystic Ovary Syndrome; Principal Investigator; Production; Progesterone; Protein Overexpression; Protocols documentation; REM Sleep; Randomized; Regulation; Reporter; Reporting; Research Design; Research Personnel; Response Elements; Risk Factors; Role; Satiation; Sex Characteristics; Signal Transduction; Skeletal Muscle; Sleep; Sleep Apnea Syndromes; Slow-Wave Sleep; Testing; Therapeutic Intervention; Time; Tissues; Triglyceride Metabolism; Triglycerides; Universities; Urine; Week; Weight; Woman; Work; acylcarnitine; adenoviral-mediated; adiponectin; base; blood glucose regulation; cardiovascular risk factor; day; design; early onset; genetic manipulation; glucose metabolism; improved; in vitro Assay; in vivo; insight; insulin secretion; insulin sensitivity; insulin signaling; insulin tolerance; lipid biosynthesis; lipid metabolism; men; metabolomics; non rapid eye movement; novel; programs; reproductive; research study; resistin; small hairpin RNA; tool; xenoestrogen

Polycystic ovary syndrome (PCOS) affects up to 10% of women of reproductive age, and is characterized by elevation in circulating androgen levels, insulin resistance, dyslipidemia and obesity. However, the molecular mechanisms that underlie the development of the metabolic syndrome in PCOS remain unclear. The interplay between PCOS and obstructive sleep apnea (OSA) in women may play a critical but under appreciated role in these pathologies. Despite the recent linkage between OSA and insulin resistance, and the finding that obese women with PCOS are up to 30 times more likely to develop OSA as weight matched women without PCOS, most of the studies on OSA and metabolism have been conducted in men. The central hypothesis of this application is that OSA is a novel risk factor for the development of insulin resistance in adipose tissue in women with PCOS. We will test this hypothesis by measuring insulin sensitivity in primary adipocytes from obese PCOS women with OSA, before and after therapeutic intervention for the OSA. Insulin signal transduction and regulation of lipid metabolism will be assayed in vitro and compared to values obtained in vivo. Additionally, we will determine the role alterations in circulating glucocorticoids and the localized activation of glucocorticoids in adipocytes by the enzyme 110- HSD1 on adipocytic insulin action. Finally, the effects of modulating reducing endogenous ovarian androgen production on insulin signaling in adipocytes from obese PCOS women with OSA will be determined, as will the effects of giving exogenous estrogen or progesterone to patients. Together, these studies will comprise an integral part of a larger SCOR application that will undertake a comprehensive examination of the role of OSA and circulating androgen on the development on insulin resistance, obesity and the metabolic syndrome in women with PCOS. Relevance: Women with PCOS suffer from obesity, metabolic syndrome, dysregulation of sex steroid synthesis and obstructive sleep apnea. However, the inter connections between these various disorders is not well understood. As part of an integrative collaborative project, this application will directly investigate the effects of OSA and androgens on insulin sensitivity in adipocyte biopsies from PCOS patients before and after therapeutic interventions.

多囊卵巢综合征（PCOS）影响多达10％的生殖年龄妇女，其特征是 循环雄激素水平，胰岛素抵抗，血脂异常和肥胖的升高。但是， PCOS代谢综合征发展的基础的分子机制尚不清楚。 PCOS与女性阻塞性睡眠呼吸暂停（OSA）之间的相互作用可能会扮演关键，但在下面 在这些病理学中欣赏的作用。尽管OSA和胰岛素抵抗之间有着最近的联系，并且 随着体重匹配，患有PCOS的肥胖女性的肥胖女性的可能性高30倍 没有PCOS的女性，大多数关于OSA和代谢的研究都是在男性中进行的。这 该应用的中心假设是OSA是开发胰岛素的新风险因素 PCOS女性脂肪组织的抗性。我们将通过测量胰岛素来检验该假设 治疗前后的肥胖PCOS妇女的原发性脂肪细胞的敏感性 OSA的干预。胰岛素信号转导和脂质代谢的调节将在 体外并与体内获得的值进行比较。此外，我们将确定角色改变 通过酶110-循环糖皮质激素和脂肪细胞中糖皮质激素的局部激活 脂肪细胞胰岛素作用的HSD1。最后，调节还原内源性卵巢雄激素的影响 将确定来自患有OSA肥胖PCOS女性的脂肪细胞中胰岛素信号传导的生产，将确定 给患者提供外源雌激素或孕激素的影响。这些研究一起将包括 较大的SCOR应用程序的组成部分，该应用将对 OSA和循环雄激素在胰岛素抵抗，肥胖和代谢方面的发育中 PCOS女性的综合征。 相关性：患有PCOS的女性患有肥胖症，代谢综合征，性类固醇失调 合成和阻塞性睡眠呼吸暂停。但是，这些各种疾病之间的相互联系是 不太了解。作为综合协作项目的一部分，该应用程序将直接调查 OSA和雄激素对PCOS患者的脂肪细胞活检中胰岛素敏感性的影响 治疗干预后。